Figure 2.

The UPR. The metazoan UPR comprises three integrated signaling pathways activated downstream of the ER membrane proteins PERK, ATF6, and IRE1. In response to ER stress, these pathways are activated through mechanisms including dissociation of the ER HSP70 chaperone BiP from their luminal domains. Once activated, UPR signaling promotes adaptive remodeling of ER proteostasis pathways and global cellular physiology through both a transient attenuation of new protein synthesis (downstream of PERK) and activation of the stress-responsive transcription factors ATF4, ATF6, and XBP1s (downstream of PERK, ATF6, and IRE1, respectively). Created with BioRender.com.